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WO2020005325A1 - Aptamères pour compositions de soin capillaire - Google Patents

Aptamères pour compositions de soin capillaire Download PDF

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Publication number
WO2020005325A1
WO2020005325A1 PCT/US2019/017151 US2019017151W WO2020005325A1 WO 2020005325 A1 WO2020005325 A1 WO 2020005325A1 US 2019017151 W US2019017151 W US 2019017151W WO 2020005325 A1 WO2020005325 A1 WO 2020005325A1
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WIPO (PCT)
Prior art keywords
hair
seq
aptamer
oligonucleotides
group
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Ceased
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PCT/US2019/017151
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English (en)
Inventor
Juan Esteban VELASQUEZ
Amy Violet Trejo
Jennifer Mary Marsh
Gregory Allen Penner
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Procter and Gamble Co
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Procter and Gamble Co
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Priority to MX2020014143A priority Critical patent/MX2020014143A/es
Priority to CN201980042900.3A priority patent/CN112384622A/zh
Priority to JP2020571775A priority patent/JP2021529743A/ja
Priority to EP19707210.1A priority patent/EP3814505A1/fr
Publication of WO2020005325A1 publication Critical patent/WO2020005325A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/16—Aptamers

Definitions

  • the present invention generally relates to nucleic acid aptamers that have a high binding affinity and specificity for damaged human hair. This invention also relates to the use of such aptamers as delivery vehicles of active ingredients to the hair.
  • Aptamers are short single-stranded oligonucleotides, with a specific and complex three- dimensional shape, that bind to target molecules.
  • the molecular recognition of aptamers is based on structure compatibility and intermolecular interactions, including electrostatic forces, van der Waals interactions, hydrogen bonding, and p-p stacking interactions of aromatic rings with the target material.
  • the targets of aptamers include, but are not limited to, peptides, proteins, nucleotides, amino acids, antibiotics, low molecular weight organic or inorganic compounds, and even whole cells.
  • the dissociation constant of aptamers typically varies between micromolar and picomolar levels, which is comparable to the affinity of antibodies to their antigens. Aptamers can also be designed to have high specificity, enabling the discrimination of target molecules from closely related derivatives.
  • Aptamers are usually designed in vitro from large libraries of random nucleic acids by Systematic Evolution of Ligands by Exponential Enrichment (SELEX).
  • SELEX Systematic Evolution of Ligands by Exponential Enrichment
  • the SELEX method is first introduced in 1990 when single stranded RNAs are selected against low molecular weight dyes (Ellington, A.D., Szostak, J. W., 1990. Nature 346: 818-822).
  • single stranded DNA aptamers and aptamers containing chemically modified nucleotides are also described (Ellington, A.D., Szostak, J.W., 1992. Nature 355: 850-852; Green, L.S., et ak, 1995. Chem. Biol. 2: 683-695).
  • aptamers for hundreds of microscopic targets such as cations, small molecules, proteins, cells, or tissues have been selected.
  • a compilation of examples from the literature is included in the database at the website: http://www.aptagen.com/aptamer- index/aptamer-list.aspx.
  • aptamers that selectively bind to hair including damaged hair.
  • an aptamer composition comprises at least one oligonucleotide consisting of: deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, and mixtures thereof; wherein said aptamer composition has a binding affinity for a material selected from the group consisting of: undamaged hair, damaged hair, hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, l8-methyleicosanoic acid, and mixtures thereof.
  • an aptamer composition is provided.
  • the aptamer composition of claim 1 may comprise at least one oligonucleotide selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, SEQ ID NO 214 to SEQ ID NO 220.
  • the aptamer composition may comprise at least one oligonucleotide comprising one or more motifs selected from the group consisting of SEQ ID NO 201 to SEQ ID NO 213.
  • a hair care composition may comprise at least one nucleic acid aptamer; wherein said at least one nucleic acid aptamer has a binding affinity for a hair component.
  • said hair component is selected from the group comprising: hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, l8-methyleicosanoic acid, and mixtures thereof.
  • a method for delivering one or more hair care active ingredients to the hair may comprise administering a hair care composition comprising at least one nucleic acid aptamer and one or more hair care active ingredients; wherein said at least one nucleic acid aptamer and said one or more hair care active ingredients are covalently or non-covalently attached; and wherein said at least one nucleic acid aptamer has a binding affinity for a hair component.
  • a method for delivering one or more hair care active ingredients to the hair may comprise administering a hair care composition comprising: at least one nucleic acid aptamer and one or more nanomaterials; wherein said at least one nucleic acid aptamer and said one or more nanomaterials are covalently or non-covalently attached; and wherein said at least one nucleic acid aptamer has a binding affinity for a hair component.
  • FIGURE 1 Aptamer selection strategy.
  • FIGURE Total number of sequences on each selection library.
  • FIGURE 3 The enrichment trajectories of the top 20 sequences in terms frequency across different selection rounds for channel A.
  • FIGURE 4 The enrichment trajectories of the top 20 sequences in terms of frequency across different selection rounds for channel B.
  • FIGURE 5 Correlation matrix ordered by clustering (Ward.D2 method) for enrichment trajectories of top 100 aptamers of channel A.
  • FIGURE 6 Correlation matrix ordered by clustering (Ward.D2 method) for enrichment trajectories of top 100 aptamers of channel B.
  • FIGURE 7 Binding of different aptamers at 50 nM to different hair samples.
  • FIGURE 8 Effect of concentration of aptamers on the total amount bound to hair sample
  • FIGURE 9 Effect of concentration of aptamers on the percentage bound to hair sample 1.
  • FIGURE 10. Effect of hair type (root versus tip) on the percentage of aptamer bound to hair sample # 18.
  • FIGURE 11 Motif analysis of random region of aptamer H-Al.
  • FIGURE 12 The predicted secondary structures of aptamer H-Al and its conserved motif.
  • FIGURE 13 Motif analysis of random region of aptamer H-A2.
  • FIGURE 14 The predicted secondary structures of aptamer H-A2 and its conserved motif.
  • FIGURE 16 The predicted secondary structures of aptamer H-Bl and its conserved motifs.
  • FIGURE 18 The predicted secondary structures of aptamer H-B2 and its conserved motif.
  • FIGURE 19 Alignment of exemplary sequences with at least 50% nucleotide sequence identity that are identified during the selection process.
  • FIGURE 20 Predicted secondary structures of truncated aptamers H-Al.l (left) and H- A1.2 (right). The conserved motif (SEQ ID NO 201) is highlighted.
  • FIGURE 21 Predicted secondary structures of truncated aptamers H-A2.1 (left) and H- A2.2 (right).
  • FIGURE 22 Predicted secondary structures of truncated aptamers H-Bl.l (left) and H-
  • FIGURE 23 Predicted secondary structure of truncated aptamers H-B2.1. The conserved motif (SEQ ID NO 212) is highlighted.
  • aptamer refers to a single stranded oligonucleotide or a peptide that has a binding affinity for a specific target.
  • nucleic acid refers to a polymer or oligomer of nucleotides. Nucleic acids are also referred as“ribonucleic acids” when the sugar moiety of the nucleotides is D-ribose and as“deoxyribonucleic acids” when the sugar moiety is 2-deoxy-D-ribose.
  • nucleotide usually refers to a compound consisting of a nucleoside esterified to a monophosphate, polyphosphate, or phosphate-derivative group via the hydroxyl group of the 5-carbon of the sugar moiety. Nucleotides are also referred as “ribonucleotides” when the sugar moiety is D-ribose and as“deoxyribonucleotides” when the sugar moiety is 2-deoxy-D-ribose.
  • nucleoside refers to a glycosylamine consisting of a nucleobase, such as a purine or pyrimidine, usually linked to a 5-carbon sugar (e.g. D-ribose or 2-deoxy-D- ribose) via a b-glycosidic linkage. Nucleosides are also referred as“ribonucleosides” when the sugar moiety is D-ribose and as“deoxyribonucleosides” when the sugar moiety is 2-deoxy-D- ribose.
  • nucleobase refers to a compound containing a nitrogen atom that has the chemical properties of a base.
  • nucleobases are compounds comprising pyridine, purine, or pyrimidine moieties, including, but not limited to adenine, guanine, hypoxanthine, thymine, cytosine, and uracil.
  • oligonucleotide refers to an oligomer composed of nucleotides.
  • the term“identical” or“sequence identity,” in the context of two or more oligonucleotides, nucleic acids, or aptamers, refers to two or more sequences that are the same or have a specified percentage of nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using sequence comparison algorithms or by visual inspection.
  • the term“substantially homologous” or“substantially identical” in the context of two or more oligonucleotides, nucleic acids, or ap tamers generally refers to two or more sequences or subsequences that have at least 40%, 60%, 80%, 90%, 95%, 96%, 97%, 98% or 99% nucleotide identity, when compared and aligned for maximum correspondence, as measured using sequence comparison algorithms or by visual inspection.
  • epitope refers to the region of a target that interacts with the aptamer.
  • An epitope can be a contiguous stretch within the target or can be represented by multiple points that are physically proximal in a folded form of the target.
  • the term“motif’ refers to the sequence of contiguous, or series of contiguous, nucleotides occurring in a library of aptamers with binding affinity towards a specific target (e.g hair) and that exhibits a statistically significant higher probability of occurrence than would be expected compared to a library of random oligonucleotides.
  • the motif sequence is frequently the result or driver of the aptamer selection process.
  • the term“Damaged hair” is hair that has been exposed to (a) a chemical treatment, such as permanent or semi-permanent coloring, permanent or semi-permanent styling, relaxers, bleaching, etc, (b) mechanically damage from repeated use of brushing or combing, (c) thermal damage from use of hair dryers and/or hot implements such as flat iron, and (d) environmental exposure to UV sunlight, bleached water, etc.
  • the natural outer hair layer (F-layer) is partially or totally removed by chemical treatments or exposure to environmental factors, making the hair fibers more hydrophilic
  • the natural weatherproofing while helping to seal in moisture and prevent further damage is removed, making the hair more prone to further chemical and/or mechanical damage.
  • Non-damaged hair is hair in its natural state that has not been significantly exposed to the above-mentioned conditions.
  • Virgin hair can he collected from people who do not use chemical treatments, heating implements, excessive brushing or significant exposure to UV light, bleached water, etc.
  • consumers’ newly emerged hair (roots) have more characteristics of virgin hair than the ends of the hair as they have less exposure to the above-mentioned conditions that damage the hair.
  • binding affinity refers to:
  • Binding affinity Amount of aptamer bound to the hair sample / Total amount of aptamer incubated with the hair sample x 100%. The higher the amount of aptamer bound to the hair sample, the higher the binding affinity under the tested conditions.
  • Nucleic acid aptamers are single- stranded oligonucleotides, with specific secondary and tertiary structures, that can bind to targets with high affinity and specificity.
  • an aptamer composition may comprise at least one oligonucleotide consisting of: deoxyribonucleo tides, ribonucleotides, derivatives of deoxyribonucleo tides, derivatives of ribonucleotides, and mixtures thereof; wherein said aptamer composition has a binding affinity for a material selected from the group consisting of: undamaged hair, damaged hair, hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, 18- methyleicosanoic acid, and mixtures thereof.
  • said aptamer composition may have a binding affinity for damaged hair.
  • said aptamer composition may have a binding affinity for a damaged hair
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 50% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200 and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 70% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200 and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 90% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200 and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprises at least one oligonucleotide selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200 and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides containing at least 10 contiguous nucleotides from sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides containing at least 20 contiguous nucleotides from sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides containing at least 30 contiguous nucleotides from sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides containing at least 40 contiguous nucleotides from sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides containing at least 60 contiguous nucleotides from sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides containing at least 70 contiguous nucleotides from sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • a non-limiting example of oligonucleotide containing at least 30 contiguous nucleotides from SEQ ID NO 1 is SEQ ID NO 213.
  • a non-limiting example of oligonucleotide containing at least 20 contiguous nucleotides from SEQ ID NO 1 is SEQ ID NO 214.
  • a non limiting example of oligonucleotide containing at least 20 contiguous nucleotides from SEQ ID NO 2 is SEQ ID NO 215.
  • a non-limiting example of oligonucleotide containing at least 30 contiguous nucleotides from SEQ ID NO 2 is SEQ ID NO 216.
  • a non-limiting example of oligonucleotide containing at least 30 contiguous nucleotides from SEQ ID NO 101 is SEQ ID NO 217.
  • oligonucleotide containing at least 20 contiguous nucleotides from SEQ ID NO 101 is SEQ ID NO 218.
  • oligonucleotide containing at least 40 contiguous nucleotides from SEQ ID NO 102 is SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 50% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 60% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 70% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, and SEQ ID NO 213 to SEQ ID NO 219.
  • said aptamer composition may comprise at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 90% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, and SEQ ID NO 213 to SEQ ID NO 219.
  • a non-limiting example of an oligonucleotide with at least 60% nucleotide sequence identity to SEQ ID NO 8 is SEQ ID NO 79.
  • a non-limiting example of an oligonucleotide with at least 60% nucleotide sequence identity to SEQ ID NO 46 is SEQ ID NO 156.
  • a non- limiting example of an oligonucleotide with at least 50% nucleotide sequence identity to SEQ ID NO 52 is SEQ ID NO 53.
  • said at least one oligonucleotide may comprise one or more motifs selected from the group consisting of SEQ ID NO 201 to SEQ ID NO 212.
  • said aptamer composition may comprise at least one oligonucleotide comprising a sequence of nucleotides with at least 70% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 201 to SEQ ID NO 212.
  • said aptamer composition may comprise at least one oligonucleotide comprising a sequence of nucleotides with at least 80% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 201 to SEQ ID NO 212.
  • said aptamer composition may comprise at least one oligonucleotide comprising a sequence of nucleotides with at least 90% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 201 to SEQ ID NO 212.
  • said at least one oligonucleotide of said aptamer composition may comprise natural or non-natural nucleobases.
  • Natural nucleobases are adenine, cytosine, guanine, thymine, and uracil.
  • Non-limiting examples of non-natural nucleobases are hypoxanthine, xanthine, 7-methylguanine, 5,6- dihydrouracil, 5-5-methylcytosine, 5-hydroxymethylcytosine, thiouracil, l-methylhypoxanthine, 6-methylisoquinoline-l-thione-2-yl, 3-methoxy-2-naphthyl, 5-propynyluracil-l-yl, 5- methylcytosin-l-yl, 2-aminoadenin-9-yl, 7-deaza-7-iodoadenin-9-yl, 7-deaza-7-propynyl-2- aminoadenin-9-yl, phenoxazinyl, phenoxazinyl-G-clam, bromouracil, 5-iodouracil, and mixtures thereof.
  • Modifications of the phosphate backbone of the oligonucleotides can also increase the resistance against nuclease digestion.
  • the nucleosides of said oligonucleotides may be linked by a chemical motif selected from the group comprising: natural phosphate diester, chiral phosphorothionate, chiral methyl phosphonate, chiral phosphoramidate, chiral phosphate chiral triester, chiral boranophosphate, chiral phosphoroselenoate, phosphorodithioate, phosphorothionate amidate, methylenemethylimino, 3 '-amide, 3' achiral phosphoramidate, 3' achiral methylene phosphonates, thioformacetal, thioethyl ether, fluorophosphate, and mixtures thereof.
  • the nucleosides of said oligonucleotides may be linked by natural phosphate diesters.
  • the sugar moiety of the nucleosides of said oligonucleotides may be selected from the group comprising: ribose, deoxyribose, 2'-fluoro deoxyribose, 2'-0-methyl ribose, 2'-0-(3- amino)propyl ribose, 2'-0-(2-methoxy)ethyl ribose, 2'-0-2-(N,N- dimethylaminooxy)ethyl ribose, 2'-0-2-[2-(N,N-dimethylamino)ethyloxy]ethyl ribose, 2'-0-N,N- dimethylacetamidyl ribose, N-morpholinophosphordiamidate, a-deoxyribofuranosyl, other pentoses, hexoses, and mixtures thereof.
  • said derivatives of ribonucleotides or said derivatives of deoxyribonucleotides may be selected from the group comprising: locked oligonucleotides, peptide oligonucleotides, glycol oligonucleotides, threose oligonucleotides, hexitol oligonucleotides, altritol oligonucleotides, butyl oligonucleotides, L-ribonucleo tides, arabino oligonucleotides, 2'- fluoroarabino oligonucleotides, cyclohexene oligonucleotides, phosphorodiamidate morpholino oligonucleotides, and mixtures thereof.
  • the nucleotides at the 5’- and 3’- ends of said at least one oligonucleotide may be inverted.
  • at least one nucleotide of said at least one oligonucleotide may be fluorinated at the 2’ position of the pentose group.
  • the pyrimidine nucleotides of said at least one oligonucleotide may be fluorinated at the 2’ position of the pentose group.
  • the aptamer composition further may comprise at least one polymeric material, wherein said at least one polymeric material is covalently linked to said at least one oligonucleotide.
  • said at least one polymeric material may be polyethylene glycol.
  • said at least one oligonucleotide may between about 10 and about 200 nucleotides in length. In the present invention, said at least one oligonucleotide may be less than about 100 nucleotides in length. In the present invention, said at least one oligonucleotide may less than about 50 nucleotides in length. In present invention, wherein said at least one oligonucleotide may be covalently or non- covalently attached to one or more hair care active ingredients. Suitable hair care active ingredients include any material that is generally considered as safe and that provides benefits to the hair, and specifically to the condition of the hair surfaces that such hair care active ingredients interact with.
  • said one or more hair care active ingredients may be selected from the group comprising: conditioning agents, brightening agents, strengthening agents, anti-fungal agents, anti-bacterial agents, anti-microbial agents, anti-dandruff agents, anti- malodor agents, perfumes, olfactory enhancement agents, anti-itch agents, cooling agents, anti adherence agents, moisturization agents, smoothness agents, surface modification agents, antioxidants, natural extracts and essential oils, dyes, pigments, bleaches, nutrients, peptides, vitamins, enzymes, chelants, and mixtures thereof.
  • said at least one oligonucleotide may be non-covalently attached to said one or more hair care active ingredients via molecular interactions.
  • molecular interactions are electrostatic forces, van der Waals interactions, hydrogen bonding, and p-p stacking interactions of aromatic rings.
  • said at least one oligonucleotide may be covalently attached to said one or more hair care active ingredients using one or more linkers or spacers.
  • linkers are chemically labile linkers, enzyme-labile linkers, and non-cleavable linkers.
  • Examples of chemically labile linkers are acid-cleavable linkers and disulfide linkers. Acid- cleavable linkers take advantage of low pH to trigger hydrolysis of an acid-cleavable bond, such as a hydrazone bond, to release the active ingredient or payload. Disulfide linkers can release the active ingredients under reducing environments.
  • enzyme-labile linkers are peptide linkers that can be cleaved in the present of proteases and b-glucuronide linkers that are cleaved by glucuronidases releasing the payload. Non-cleavable linkers can also release the active ingredient if the aptamer is degraded by nucleases.
  • said at least one oligonucleotide may be covalently or non- covalently attached to one or more nanomaterials.
  • said at least one oligonucleotide and said one or more hair care active ingredients may be covalently or non- covalently attached to one or more nanomaterials.
  • said one or more hair care active ingredients may be carried by said one or more nanomaterials.
  • Nanomaterials are gold nanoparticles, nano-scale iron oxides, carbon nanomaterials (such as single-walled carbon nanotubes and graphene oxide), mesoporous silica nanoparticles, quantum dots, liposomes, poly (lactide-co-glycolic acids) nanoparticles, polymeric micelles, dendrimers, serum albumin nanoparticles, and DNA-based nanomaterials.
  • These nanomaterials can serve as carriers for large volumes of hair care active ingredients, while the aptamers can facilitate the delivery of the nanomaterials with the actives to the expected target.
  • Nanomaterials can have a variety of shapes or morphologies. Non-limiting examples of shapes or morphologies are spheres, rectangles, polygons, disks, toroids, cones, pyramids, rods/cylinders, and fibers. In the context of the present invention, nanomaterials usually have at least one spatial dimension that is less than about 100 pm and more preferably less than about 10 pm. Nanomaterials comprise materials in solid phase, semi-solid phase, or liquid phase.
  • an aptamer composition may comprise at least one peptide or protein; wherein said aptamer composition has a binding affinity for a material selected from the group consisting of: undamaged hair, damaged hair, hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, 18- methyleicosanoic acid, and mixtures thereof.
  • SELEX Systematic Evolution of Ligands by Exponential Enrichment
  • the bound sequences are eluted and amplified by PCR to prepare for subsequent rounds of selection in which the stringency of the elution conditions is usually increased to identify the tightest-binding oligonucleotides.
  • improved versions such as capillary electrophoresis-SELEX, magnetic bead- based SELEX, cell-SELEX, automated SELEX, complex-target SELEX, among others.
  • a review of aptamer screening methods is found in“Kim, Y. S. and M. B. Gu (2014). Advances in Aptamer Screening and Small Molecule Aptasensors. Adv. Biochem. Eng./Biotechnol.
  • SELEX-A Revolutionary method to generate high-affinity nucleic acid ligands. Biomol. Eng. 24(4): 381- 403,” the contents of which are incorporated herein by reference. Although the SELEX method has been broadly applied, it is neither predictive nor standardized for every target. Instead, a method must be developed for each particular target in order for the method to lead to viable aptamers.
  • the initial candidate library is generally a mixture of chemically synthesized DNA oligonucleotides, each comprising a long variable region of n nucleotides flanked, at the 3' and 5' ends, by conserved regions or primer recognition regions for all the candidates of the library. These primer recognition regions allow the central variable region to be manipulated during SELEX, in particular by means of PCR.
  • the length of the variable region determines the diversity of the library, which is equal to 4 n since each position can be occupied by one of four nucleotides A, T, G or C.
  • n 50
  • the theoretical diversity is 4 50 or 10 30 , which is an inaccessible value in practice as it corresponds to more than 10 5 tons of material for a library wherein each sequence is represented once.
  • the experimental limit is around 10 15 different sequences, which is that of a library wherein all candidates having a variable region of 25 nucleotides are represented. If one chooses to manipulate a library comprising a 30-nucleotide variable region whose theoretical diversity is about 10 18 , only 1/1000 of the possibilities will thus be explored.
  • the starting mixture of oligonucleotides may comprise more than about 10 6 different oligonucleotides and more preferably between about 10 13 to about 10 15 different oligonucleotides.
  • the length of the variable region may be between about 10 and about 100 nucleotides. In the present invention, the length of the variable region may be between about 20 and about 60 nucleotides. In the present invention, the length of the variable region may be about 40 nucleotides. Random regions shorter than 10 nucleotides may be used, but may be constrained in their ability to form secondary or tertiary structures and in their ability to bind to target molecules.
  • Random regions longer than 100 nucleotides may also be used but may present difficulties in terms of cost of synthesis.
  • the randomness of the variable region is not a constraint of the present invention. For instance, if previous knowledge exists regarding oligonucleotides that bind to a given target, libraries spiked with such sequences may work as well or better than completely random ones.
  • the length of primer recognition sequences may be between about 10 and about 40 nucleotides. In the present invention, the length of primer recognition sequences may be between about 12 and about 30 nucleotides. In the present invention, the length of primer recognition sequences may be between about 18 and about 26 nucleotides, i.e., about 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides. The length and sequence of the primer recognition sequences determine their annealing temperature. In the present invention, the primer recognition sequences of said oligonucleotides may have an annealing temperature between about 60 °C and about 72 °C.
  • RNA ribonucleotides
  • DNA deoxynucleotides
  • the first SELEX step may consist in transcribing the initial mixture of chemically synthesized DNA oligonucleotides via the primer recognition sequence at the 5' end. After selection, the candidates are converted back into DNA by reverse transcription before being amplified.
  • RNA and DNA aptamers having comparable characteristics have been selected against the same target and reported in the art. Additionally, both types of aptamers can be competitive inhibitors of one another, suggesting potential overlapping of interaction sites.
  • New functionalities such as hydrophobicity or photoreactivity, can be incorporated into the oligonucleotides by modifications of the nucleobases before or after selection. Modifications at the C-5 position of pyrimidines or at the C-8 or N-7 positions of purines are especially common and compatible with certain enzymes used during the amplification step in SELEX.
  • said oligonucleotides may comprise natural or non-natural nucleobases. Natural nucleobases are adenine, cytosine, guanine, thymine, and uracil.
  • Non-limiting examples of non natural nucleobases are hypoxanthine, xanthine, 7-methylguanine, 5,6-dihydrouracil, 5-5- methylcytosine, 5-hydroxymethylcytosine, thiouracil, l-methylhypoxanthine, 6- methylisoquinoline-l-thione-2-yl, 3-methoxy-2-naphthyl, 5-propynyluracil-l-yl, 5- methylcytosin-l-yl, 2-aminoadenin-9-yl, 7-deaza-7-iodoadenin-9-yl, 7-deaza-7-propynyl-2- aminoadenin-9-yl, phenoxazinyl, phenoxazinyl-G-clam, 5-bromouracil, 5-iodouracil, and mixtures thereof.
  • the nucleosides of said oligonucleotides may be linked by a chemical motif selected from the group comprising: natural phosphate diester, chiral phosphorothionate, chiral methyl phosphonate, chiral phosphoramidate, chiral phosphate chiral triester, chiral boranophosphate, chiral phosphoroselenoate, phosphorodithioate, phosphorothionate amidate, methylenemethylimino, 3 '-amide, 3' achiral phosphoramidate, 3' achiral methylene phosphonates, thioformacetal, thioethyl ether, fluorophosphate, and mixtures thereof.
  • the nucleosides of said oligonucleotides may be linked by natural phosphate diesters.
  • the sugar moiety of the nucleosides of said oligonucleotides may be selected from the group comprising: ribose, deoxyribose, 2'-fluoro deoxyribose, 2'-0-methyl ribose, 2'-0-(3- amino)propyl ribose, 2'-0-(2-methoxy)ethyl ribose, 2'-0-2-(N,N- dimethylaminooxy)ethyl ribose, 2'-0-2-[2-(N,N-dimethylamino)ethyloxy]ethyl ribose, 2'-0-N,N- dimethylacetamidyl ribose, N-morpholinophosphordiamidate, a-deoxyribofuranosyl, other pentoses, hexoses, and mixtures thereof.
  • said derivatives of ribonucleotides or said derivatives of deoxyribonucleotides may be selected from the group comprising: locked oligonucleotides, peptide oligonucleotides, glycol oligonucleotides, threose oligonucleotides, hexitol oligonucleotides, altritol oligonucleotides, butyl oligonucleotides, L-ribonucleo tides, arabino oligonucleotides, 2'- fluoroarabino oligonucleotides, cyclohexene oligonucleotides, phosphorodiamidate morpholino oligonucleotides, and mixtures thereof.
  • modified nucleotides When using modified nucleotides during the SELEX process, they should be compatible with the enzymes used during the amplification step.
  • modifications that are compatible with commercial enzymes include modifications at the 2’ position of the sugar in RNA libraries.
  • the ribose 2’-OH group of pyrimidine nucleotides can be replaced with 2’-amino, 2’-fluoro, 2’-methyl, or 2’-0-methyl, which protect the RNA from degradation by nucleases.
  • Additional modifications in the phosphate linker such as phosphorothionate and boranophosphate, are also compatible with the polymerases and confer resistance to nucleases.
  • At least one nucleotide of said oligonucleotides may be fluorinated at the 2’ position of the pentose group.
  • the pyrimidine nucleotides of said oligonucleotides may be at least partially fluorinated at the 2’ position of the pentose group.
  • all the pyrimidine nucleotides of said oligonucleotides may be fluorinated at the 2’ position of the pentose group.
  • at least one nucleotide of said oligonucleotides may be am mated at the 2’ position of the pentose group.
  • DCC dynamic combinatorial chemistry
  • Natural oligonucleotides are D-isomers. L-analogs are resistant to nucleases but cannot be synthesized by polymerases. According to the laws of optical isomerism, an L-series aptamer can form with its target (T) a complex having the same characteristics as the complex formed by the D-series isomer and the enantiomer (T') of the target (T). Consequently, if compound T' can be chemically synthesized, it can be used to perform the selection of a natural aptamer (D). Once identified, this aptamer can be chemically synthesized in an L-series. This L-aptamer is a ligand of the natural target (T).
  • the initial sequence library is thus a library of three- dimensional shapes, each corresponding to a distribution of units that can trigger electrostatic interactions, create hydrogen bonds, etc. Selection becomes a question of identifying in the library the shape suited to the target, i.e., the shape allowing the greatest number of interactions and the formation of the most stable aptamer-target complex.
  • the aptamers identified are characterized by equilibrium dissociation constants in the micromolar range, whereas for protein targets K d values below 10 -9 M are not rare.
  • Selection in each round occurs by means of physical separation of oligonucleotides associated with the target from free oligonucleotides. Multiple techniques may be applied (chromatography, filter retention, electrophoresis, etc.). The selection conditions are adjusted (relative concentration of target/candidates, ion concentration, temperature, washing, etc.) so that a target-binding competition occurs between the oligonucleotides. Generally, stringency is increased as the rounds proceed in order to promote the capture of oligonucleotides with the highest affinity. In addition, counter- selections or negative selections are carried out to eliminate oligonucleotides that recognize the support or unwanted targets (e.g., filter, beads, etc.).
  • targets e.g., filter, beads, etc.
  • the SELEX process for the selection of target-specific aptamers is characterized by repetition of five main steps: binding of oligonucleotides to the target, partition or removal of oligonucleotides with low binding affinity, elution of oligonucleotides with high binding affinity, amplification or replication of oligonucleotides with high binding affinity, and conditioning or preparation of the oligonucleotides for the next cycle.
  • This selection process is designed to identify the oligonucleotides with the greatest affinity and specificity for the target material.
  • a method of designing an aptamer composition may comprise the step of contacting: a) a mixture of oligonucleotides, b) a selection buffer, and c) a target material selected from the group consisting of: undamaged hair, damaged hair, hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, 18- methyleicosanoic acid, and mixtures thereof.
  • said target material may be selected from the group consisting of: undamaged hair, damaged hair, and mixtures thereof.
  • said target material may be damaged hair.
  • said mixture of oligonucleotides comprises oligonucleotides may be selected from the group consisting of deoxyribonucleo tides, ribonucleotides, derivatives of deoxyribonucleo tides, derivatives of ribonucleotides, and mixtures thereof.
  • SELEX cycles are usually repeated several times until oligonucleotides with high binding affinity are identified.
  • the number of cycles depends on multiple variables, including target features and concentration, design of the starting random oligonucleotide library, selection conditions, ratio of target binding sites to oligonucleotides, and the efficiency of the partitioning step.
  • said contacting step may be performed at least 5 times. In the present invention, said contacting step may be performed between 6 and 15 times.
  • said method may further comprise the step of removing the oligonucleotides that do not bind said target material during said contacting step.
  • Oligonucleotides are oligo-anions, each unit having a charge and hydrogen-bond donor/acceptor sites at a particular pH.
  • the pH and ionic strength of the selection buffer are important and should represent the conditions of the intended aptamer application.
  • the pH of said selection buffer may be between about 2 and about 9.
  • the pH of said selection buffer may be between about 5 and about 8.
  • said selection buffer may comprise cations.
  • Non-limiting examples of cations are Mg 2+ , Ca 2+ , Sn 2+ , Sn 4+ , Zn 2+ , Al 3+ , Cu 2+ , Fe 2+ , and Fe 3+ .
  • said selection buffer may comprise a solution or suspension of a hair care composition selected from the group comprising shampoos, conditioning shampoos, pet shampoo, leave-in treatments, sprays, liquids, pastes, Newtonian or non-Newtonian fluids, gels, and sols.
  • said selection buffer may comprise a solution of a shampoo.
  • said selection buffer may comprise at least one surfactant.
  • said at least one surfactant may be selected from the group consisting of anionic surfactants, amphoteric or zwitterionic surfactants, and mixtures thereof.
  • anionic surfactants are alkyl and alkyl ether sulfates or sulfonates, including ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanol amine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth s
  • Non-limiting amphoteric surfactants include those surfactants broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate, or phosphonate, including cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate, lauroamphodiacetate, and mixtures thereof.
  • Non-limiting examples of zwitterionic surfactants include those surfactants broadly described as derivatives of aliphatic quaternaryammonium, phosphonium, and sulfonium compounds, in which the aliphatic radicals can be straight or branched chain, and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate or phosphonate, and betaines.
  • said selection buffer may comprise at least one material selected from the group compressing: aqueous carriers, gel matrixes, silicone conditioning agents, organic conditioning materials, non-ionic polymers, deposition aids, rheology modifier / suspending agents, benefit agents, and mixtures thereof.
  • aqueous carriers are water and water solutions of lower alkyl alcohols and polyhydric alcohols, including ethanol, isopropanol, propylene glycol, hexylene glycol, glycerin, and propane diol.
  • Non-limiting examples of gel matrixes include water solutions of fatty alcohols, including cetyl alcohol, stearyl alcohol, behenyl alcohol, and mixtures thereof.
  • Non-limiting examples of silicone conditioning agents include dimethicones, dimethiconols, cyclic silicones, methylphenyl polysiloxane, and modified silicones with various functional groups such as amino groups, quaternary ammonium salt groups, aliphatic groups, alcohol groups, carboxylic acid groups, ether groups, sugar or polysaccharide groups, fluorine-modified alkyl groups, alkoxy groups, or combinations of such groups.
  • Non-limiting examples of organic conditioning materials include hydrocarbon oils, polyolefins, fatty esters, fluorinated conditioning compounds, fatty alcohols, alkyl glucosides and alkyl glucoside derivatives, quaternary ammonium compounds, polyethylene glycols and polypropylene glycols having a molecular weight of up to about 2,000,000 including those with CTFA names PEG-200, PEG-400, PEG-600, PEG- 1000, PEG-2M, PEG-7M, PEG-14M, PEG- 45M and mixtures thereof.
  • Non-limiting examples of non-ionic polymers include polyalkylene glycols, such as polyethylene glycols.
  • Non-limiting examples of deposition aids include copolymers of vinyl monomers having cationic amine or quaternary ammonium functionalities with water soluble spacer monomers such as acrylamide, methacrylamide, alkyl and dialkyl acrylamides, alkyl and dialkyl methacrylamides, alkyl acrylate, alkyl methacrylate, vinyl caprolactone, and vinyl pyrrolidone; vinyl esters, vinyl alcohol (made by hydrolysis of polyvinyl acetate), maleic anhydride, propylene glycol, and ethylene glycol, cationic celluloses, cationic starches, and cationic guar gums.
  • water soluble spacer monomers such as acrylamide, methacrylamide, alkyl and dialkyl acrylamides, alkyl and dialkyl methacrylamides, alkyl acrylate, alkyl methacrylate, vinyl caprolactone, and vinyl pyrrolidone
  • vinyl esters vinyl alcohol (made by hydro
  • Non-limiting examples of rheology modifier / suspending agents include homopolymers based on acrylic acid, methacrylic acid or other related derivatives; alginic acid-based materials; and cellulose derivatives.
  • Non-limiting examples of benefit agents include brightening agents, strengthening agents, anti-fungal agents, anti-bacterial agents, anti-microbial agents, anti-dandruff agents, anti-malodor agents, perfumes, olfactory enhancement agents, anti itch agents, cooling agents, anti- adherence agents, moisturization agents, smoothness agents, surface modification agents, antioxidants, natural extracts and essential oils, dyes, pigments, bleaches, nutrients, peptides, vitamins, enzymes, chelants, and mixtures thereof.
  • Negative selection or counter- selection steps can minimize the enrichment of oligonucleotides that bind to undesired targets or undesired epitopes within a target.
  • said method of designing an aptamer composition may further comprise the step of contacting: a) a mixture of oligonucleotides, b) a selection buffer, and c) undamaged hair.
  • the method of designing an aptamer composition may comprise the steps of: a) synthesizing a mixture of oligonucleotides; b) contacting: i. said mixture of oligonucleotides, ii. a selection buffer, and iii.
  • a target material selected from the group consisting of: undamaged hair, damaged hair, hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, l8-methyleicosanoic acid, and mixtures thereof, to produce a target suspension; c) removing the liquid phase from said target suspension to produce a target-oligonucleotide mixture; d) contacting said target-oligonucleotide mixture with a washing buffer and removing the liquid phase to produce a target-aptamer mixture; and e) contacting said target- aptamer mixture with an elution buffer and recovering the liquid phase to produce an aptamer mixture.
  • said steps may be performed repetitively at least 5 times. In the present invention, said steps may be performed between 6 and 15 times.
  • the method of designing an aptamer composition may comprise the steps of: a) synthesizing a random mixture of deoxyribonucleotides comprising oligonucleotides consisting of: i. a T7 promoter sequence at the 5’-end, ii. a variable 40-nucleotide sequence in the middle, and iii. a conserved reverse primer recognition sequence at the 3’end; b) contacting: i. said random mixture of deoxyribonucleotides, ii. a selection buffer, and iii.
  • a sample of hair to produce a target suspension; c) removing the liquid phase from said target suspension to produce a hair-oligonucleotide mixture; d) contacting said hair-oligonucleotide mixture with a washing buffer and removing the liquid phase to produce a hair-aptamer mixture; e) contacting said hair-aptamer mixture with an elution buffer and recovering the liquid phase to produce a DNA aptamer mixture; f) amplifying said DNA aptamer mixture to produce an enriched mixture of deoxyribonucleotides; and g) sequencing said enriched mixture of deoxyribonucleotides.
  • the 2’ -OH groups of the ribose moieties can be replaced by 2’-fluoro, 2’-amino, or 2’-0-methyl groups.
  • the 3’- and 5’- ends of the aptamers can be capped with different groups, such as streptavidin-biotin, inverted thymidine, amine, phosphate, polyethylene-glycol, cholesterol, fatty acids, proteins, enzymes, fluorophores, among others, making the oligonucleotides resistant to exonucleases or providing some additional benefits.
  • Other modifications are described in previous sections of the present disclosure.
  • one or more hair care active ingredients may be covalently attached to the 3’- end of said at least one oligonucleotide.
  • one or more hair care active ingredients may be covalently attached to the 5’- end of said at least one oligonucleotide.
  • one or more hair care active ingredients may be covalently attached to random positions of said at least one oligonucleotide.
  • TdT terminal deoxynucleotidyl transferases
  • PNK T4 polynucleotide kinases
  • DNA polymerases DNA polymerases
  • RNA polymerases and other enzymes known by those skilled in the art.
  • TdTs are template-independent polymerases that can add modified deoxynucleotides to the 3’ terminus of deoxyribonucleotides.
  • T4 RNA ligases can be used to label ribonucleotides at the 3’ - end by using appropriately modified nucleoside 3’,5’-bisphosphates.
  • PNK can be used to phosphorylate the 5’- end of synthetic oligonucleotides, enabling other chemical transformations (see below).
  • DNA and RNA polymerases are commonly used for the random incorporation of modified nucleotides throughout the sequence, provided such nucleotides are compatible with the enzymes.
  • Non-limiting examples of chemical methods used for modification of aptamers are periodate oxidation of ribonucleotides, EDC activation of 5’-phosphate, random chemical labeling methods, and other chemical methods known by those skilled in the art, incorporated herein as for the current invention.
  • RNA aptamers During periodate oxidation, meta- and ortho-perdionates cleave the C-C bonds between vicinal diols of 3’-ribonucleotides, creating two aldehyde moieties that enable the conjugation of labels or active ingredients at the 3’- end of RNA aptamers.
  • the resulting aldehydes can be easily reacted with hydrazide- or primary amine- containing molecules. When amines are used, the produced Schiff bases can be reduced to more stable secondary amines with sodium cyanoborohydride (NaBH 4 ).
  • the 5’-phosphate of oligonucleotides is frequently activated with EDC (l-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride) and imidazole to produce a reactive imidazolide intermediate, followed by reaction with a primary amine to generate aptamers modified at the 5’end. Because the 5’ phosphate group is required for the reaction, synthetic oligonucleotides can be first treated with a kinase (e.g. PNK).
  • a kinase e.g. PNK
  • Random chemical labeling can be performed with different methods. Because they allow labeling at random sites along the aptamer, a higher degree of modification can be achieved compared to end-labeling methods. However, since the nucleobases are modified, binding of the aptamers to their target can be disrupted.
  • the most common random chemical modification methods involve the use of photoreactive reagents, such as phenylazide-based reagents. When the phenylazide group is exposed to UV light, it forms a labile nitrene that reacts with double bonds and C-H and N-H sites of the aptamers.
  • sequence truncations can be performed to remove regions that are not essential for binding or for folding into the structure.
  • aptamers can be linked together to provide different features or better affinity. Thus, any truncations or combinations of the aptamers described herein are incorporated as part of the current invention.
  • the aptamers of the current invention can be used in hair care compositions to provide one or more benefits.
  • the hair care composition of the present invention can be a shampoo.
  • the shampoo composition comprises from about .001% to about 1%, alternatively from about .01% to about 0.5%, alternatively from about 0.1% to about 0.3% of one or more aptamer.
  • the shampoo composition may comprise one or more detersive surfactants, which provides cleaning performance to the composition.
  • the one or more detersive surfactants in turn may comprise an anionic surfactant, amphoteric or zwitterionic surfactants, or mixtures thereof.
  • detersive surfactants are set forth in U.S. Patent No. 6,649,155; U.S. Patent Application Publication No. 2008/0317698; and U.S. Patent Application Publication No. 2008/0206355, which are incorporated herein by reference in their entirety.
  • the concentration of the detersive surfactant component in the shampoo composition should be sufficient to provide the desired cleaning and lather performance, and generally ranges from about 2 wt% to about 50 wt%, from about 5 wt% to about 30 wt%, from about 8 wt% to about 25 wt%, from about 10 wt% to about 20 wt%, about 5 wt%, about 10 wt%, about 12 wt%, about 15 wt%, about 17 wt%, about 18 wt%, or about 20 wt%.
  • Anionic surfactants suitable for use in the compositions are the alkyl and alkyl ether sulfates.
  • Other suitable anionic surfactants are the water-soluble salts of organic, sulfuric acid reaction products.
  • Still other suitable anionic surfactants are the reaction products of fatty acids esterified with isethionic acid and neutralized with sodium hydroxide.
  • Other similar anionic surfactants are described in U.S. Patent Nos. 2,486,921; 2,486,922; and 2,396,278, which are incorporated herein by reference in their entirety.
  • Exemplary anionic surfactants for use in the shampoo composition include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanol amine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate, ammonium
  • Suitable amphoteric or zwitterionic surfactants for use in the shampoo composition herein include those which are known for use in shampoo or other personal care cleansing. Concentrations of such amphoteric surfactants range from about 0.5 wt% to about 20 wt%, and from about 1 wt% to about 10 wt%. Non limiting examples of suitable zwitterionic or amphoteric surfactants are described in U.S. Patent Nos. 5,104,646 and 5,106,609, which are incorporated herein by reference in their entirety.
  • Amphoteric detersive surfactants suitable for use in the shampoo composition include those surfactants broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • Exemplary amphoteric detersive surfactants for use in the present shampoo composition include cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate, lauroamphodiacetate, and mixtures thereof.
  • Zwitterionic detersive surfactants suitable for use in the shampoo composition include those surfactants broadly described as derivatives of aliphatic quatemaryammonium, phosphonium, and sulfonium compounds, in which the aliphatic radicals can be straight or branched chain, and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate or phosphonate.
  • zwitterionics such as betaines may be selected.
  • Non limiting examples of other anionic, zwitterionic, amphoteric or optional additional surfactants suitable for use in the shampoo composition are described in McCutcheon’s, Emulsifiers and Detergents, 1989 Annual, published by M. C. Publishing Co., and U.S. Patent Nos. 3,929,678, 2,658,072; 2,438,091; 2,528,378, which are incorporated herein by reference in their entirety.
  • the shampoo composition may also comprise a shampoo gel matrix, an aqueous carrier, and other additional ingredients described herein.
  • AQUEOUS CARRIER AQUEOUS CARRIER
  • the shampoo composition comprises an aqueous carrier.
  • the formulations of the shampoo composition can be in the form of pourable liquids (under ambient conditions).
  • Such compositions will therefore typically comprise an aqueous carrier, which is present at a level of at least 20 wt%, from about 20 wt% to about 95 wt%, or from about 60 wt% to about 85 wt%.
  • the aqueous carrier may comprise water, or a miscible mixture of water and organic solvent, and in one aspect may comprise water with minimal or no significant concentrations of organic solvent, except as otherwise incidentally incorporated into the composition as minor ingredients of other components.
  • the aqueous carriers useful in the shampoo composition include water and water solutions of lower alkyl alcohols and polyhydric alcohols.
  • the lower alkyl alcohols useful herein are monohydric alcohols having 1 to 6 carbons, in one aspect, ethanol and isopropanol.
  • the polyhydric alcohols useful herein include propylene glycol, hexylene glycol, glycerin, and propane diol.
  • the hair care composition of the present invention can be a hair conditioner.
  • the hair conditioner composition described herein comprises (i) from about .001% to about 1%, alternatively from about .01% to about 0.5%, alternatively from about 0.1% to about 0.3% of one or more aptamer.
  • the conditioner composition may also comprise a conditioner gel matrix comprising (1) one or more high melting point fatty compounds, (2) a cationic surfactant system, and (3) a second aqueous carrier.
  • the conditioner gel matrix of the conditioner composition includes a cationic surfactant system.
  • the cationic surfactant system can be one cationic surfactant or a mixture of two or more cationic surfactants.
  • the cationic surfactant system can be selected from: mono-long alkyl quaternized ammonium salt; a combination of mono-long alkyl quaternized ammonium salt and di-long alkyl quaternized ammonium salt; mono-long alkyl amidoamine salt; a combination of mono-long alkyl amidoamine salt and di-long alkyl quaternized ammonium salt, a combination of mono-long alkyl amindoamine salt and mono-long alkyl quaternized ammonium salt.
  • the cationic surfactant system can be included in the composition at a level by weight of from about 0.1% to about 10%, from about 0.5% to about 8%, from about 0.8 % to about 5%, and from about 1.0% to about 4%.
  • the monoalkyl quaternized ammonium salt cationic surfactants useful herein are those having one long alkyl chain which has about 22 carbon atoms and in may be a C22 alkyl group.
  • the remaining groups attached to nitrogen are independently selected from an alkyl group of from 1 to about 4 carbon atoms or an alkoxy, polyoxyalkylene, alkylamido, hydroxyalkyl, aryl or alkylaryl group having up to about 4 carbon atoms.
  • Mono-long alkyl quaternized ammonium salts useful herein are those having the formula
  • R 75 , R 76 , R 77 and R 78 is selected from an alkyl group of 22 carbon atoms or an aromatic, alkoxy, polyoxyalkylene, alkylamido, hydroxyalkyl, aryl or alkylaryl group having up to about 30 carbon atoms; the remainder of R 75 , R 76 , R 77 and R 78 are independently selected from an alkyl group of from 1 to about 4 carbon atoms or an alkoxy, polyoxyalkylene, alkylamido, hydroxyalkyl, aryl or alkylaryl group having up to about 4 carbon atoms; and X is a salt-forming anion such as those selected from halogen, (e.g.
  • alkyl groups can contain, in addition to carbon and hydrogen atoms, ether and/or ester linkages, and other groups such as amino groups.
  • the longer chain alkyl groups e.g., those of about 22 carbons, or higher, can be saturated or unsaturated.
  • R 75 , R 76 , R 77 and R 78 can be selected from an alkyl group of about 22 carbon atoms, the remainder of R 75 , R 76 , R 77 and R 78 are independently selected from CH 3 , C 2 H 5 , C 2 H 4 OH, and mixtures thereof; and X is selected from the group consisting of Cl, Br, CH 3 OSO 3 , C 2 H 5 OSO 3 , and mixtures thereof.
  • Nonlimiting examples of such mono-long alkyl quaternized ammonium salt cationic surfactants include: behenyl trimethyl ammonium salt.
  • Mono-long alkyl amines are also suitable as cationic surfactants.
  • Primary, secondary, and tertiary fatty amines are useful. Particularly useful are tertiary ami do amines having an alkyl group of about 22 carbons.
  • Exemplary tertiary a i do amines include: behenamidopropyldimethylamine, behenamidopropyldiethylamine, behenamidoethyldiethylamine, behenamidoethyldimethylamin.
  • Useful amines in the present invention are disclosed in U.S. Patent 4,275,055, Nachtigal, et al.
  • amines can also be used in combination with acids such as /’-glutamic acid, lactic acid, hydrochloric acid, malic acid, succinic acid, acetic acid, fumaric acid, tartaric acid, citric acid, i- glutamic hydrochloride, maleic acid, and mixtures thereof; and may be /’-glutamic acid, lactic acid, and/or citric acid.
  • the amines herein can be partially neutralized with any of the acids at a molar ratio of the amine to the acid of from about 1 : 0.3 to about 1 : 2, and/or from about 1 : 0.4 to about 1 : 1.
  • Di-long alkyl quaternized ammonium salt can be combined with a mono-long alkyl quaternized ammonium salt or mono-long alkyl amidoamine salt. It is believed that such combination can provide easy-to rinse feel, compared to single use of a monoalkyl quaternized ammonium salt or mono-long alkyl amidoamine salt.
  • the di-long alkyl quaternized ammonium salts are used at a level such that the wt% of the dialkyl quaternized ammonium salt in the cationic surfactant system is in the range of from about 10% to about 50%, and/or from about 30% to about 45%.
  • the di-long alkyl quaternized ammonium salt cationic surfactants useful herein are those having two long alkyl chains having about 22 carbon atoms.
  • the remaining groups attached to nitrogen are independently selected from an alkyl group of from 1 to about 4 carbon atoms or an alkoxy, polyoxyalkylene, alkylamido, hydroxyalkyl, aryl or alkylaryl group having up to about 4 carbon atoms.
  • Di-long alkyl quaternized ammonium salts useful herein are those having the formula (II):
  • R 75 , R 76 , R 77 and R 78 is selected from an alkyl group of from 22 carbon atoms or an aromatic, alkoxy, polyoxyalkylene, alkylamido, hydroxyalkyl, aryl or alkylaryl group having up to about 30 carbon atoms; the remainder of R 75 , R 76 , R 77 and R 78 are independently selected from an alkyl group of from 1 to about 4 carbon atoms or an alkoxy, polyoxyalkylene, alkylamido, hydroxyalkyl, aryl or alkylaryl group having up to about 4 carbon atoms; and X is a salt-forming anion such as those selected from halogen, (e.g.
  • alkyl groups can contain, in addition to carbon and hydrogen atoms, ether and/or ester linkages, and other groups such as amino groups.
  • the longer chain alkyl groups e.g., those of about 22 carbons, or higher, can be saturated or unsaturated.
  • R 75 , R 76 , R 77 and R 78 can be selected from an alkyl group of from 22 carbon atoms, the remainder of R 75 , R 76 , R 77 and R 78 are independently selected from C3 ⁇ 4, C2H5, C2H4OH, and mixtures thereof; and X is selected from the group consisting of Cl, Br, CH3OSO3, C2H5OSO3, and mixtures thereof.
  • dialkyl quatemized ammonium salt cationic surfactants include, for example, dialkyl (C22) dimethyl ammonium chloride, ditallow alkyl dimethyl ammonium chloride, dihydrogenated tallow alkyl dimethyl ammonium chloride.
  • dialkyl quatemized ammonium salt cationic surfactants also include, for example, asymmetric dialkyl quatemized ammonium salt cationic surfactants.
  • the conditioner gel matrix of the conditioner composition includes one or more high melting point fatty compounds.
  • the high melting point fatty compounds useful herein may have a melting point of 25 °C or higher, and is selected from the group consisting of fatty alcohols, fatty acids, fatty alcohol derivatives, fatty acid derivatives, and mixtures thereof. It is understood by the artisan that the compounds disclosed in this section of the specification can in some instances fall into more than one classification, e.g., some fatty alcohol derivatives can also be classified as fatty acid derivatives. However, a given classification is not intended to be a limitation on that particular compound, but is done so for convenience of classification and nomenclature.
  • certain compounds having certain carbon atoms may have a melting point of less than 25 °C. Such compounds of low melting point are not intended to be included in this section.
  • Nonlimiting examples of the high melting point compounds are found in International Cosmetic Ingredient Dictionary, Fifth Edition, 1993, and CTFA Cosmetic Ingredient Handbook, Second Edition, 1992.
  • fatty alcohols are suitable for use in the conditioner composition.
  • the fatty alcohols useful herein are those having from about 14 to about 30 carbon atoms, from about 16 to about 22 carbon atoms. These fatty alcohols are saturated and can be straight or branched chain alcohols. Suitable fatty alcohols include, for example, cetyl alcohol, stearyl alcohol, behenyl alcohol, and mixtures thereof.
  • High melting point fatty compounds of a single compound of high purity can be used.
  • Single compounds of pure fatty alcohols selected from the group of pure cetyl alcohol, stearyl alcohol, and behenyl alcohol can also be used.
  • pure herein, what is meant is that the compound has a purity of at least about 90%, and/or at least about 95%.
  • the high melting point fatty compound can be included in the conditioner composition at a level of from about 0.1% to about 20%, alternatively from about 1% to about 15%, and alternatively from about 1.5% to about 8% by weight of the composition, in view of providing improved conditioning benefits such as slippery feel during the application to wet hair, softness and moisturized feel on dry hair.
  • the conditioner gel matrix of the conditioner composition includes an aqueous carrier.
  • the formulations of the conditioner composition can be in the form of pourable liquids (under ambient conditions).
  • Such compositions will therefore typically comprise a second aqueous carrier, which is present at a level of from about 20 wt% to about 95 wt%, or from about 60 wt% to about 85 wt%.
  • the aqueous carrier may comprise water, or a miscible mixture of water and organic solvent, and in one aspect may comprise water with minimal or no significant concentrations of organic solvent, except as otherwise incidentally incorporated into the composition as minor ingredients of other components.
  • the aqueous carriers useful in the conditioner composition include water and water solutions of lower alkyl alcohols and polyhydric alcohols.
  • the lower alkyl alcohols useful herein are monohydric alcohols having 1 to 6 carbons, in one aspect, ethanol and isopropanol.
  • the polyhydric alcohols useful herein include propylene glycol, hexylene glycol, glycerin, and propane diol.
  • the hair care composition of the present invention can be leave-on treatment.
  • the leave-on treatment composition described herein may comprise from about .001% to about 1%, alternatively from about .01% to about 0.5%, alternatively from about 0.1% to about 0.3% of one or more aptamer.
  • the leave-on treatment may also comprises (1) one or more rheology modifiers and (2) an aqueous carrier.
  • the leave-on treatment may include one or more rheology modifiers to adjust the rheological characteristics of the composition for better feel, in-use properties and the suspending stability of the composition.
  • the rheological properties are adjusted so that the composition remains uniform during its storage and transportation and it does not drip undesirably onto other areas of the body, clothing or home furnishings during its use.
  • Any suitable rheology modifier can be used.
  • the leave-on treatment may comprise from about 0.01 % to about 3 % of a rheology modifier, alternatively from about 0.1 % to about 1 % of a rheology modifier,
  • the one or more rheology modifier may be selected from the group consisting of polyacrylamide thickeners, cationically modified polysaccharides, associative thickeners, and mixtures thereof.
  • Associative thickeners include a variety of material classes such as, for example: hydrophobic ally modified cellulose derivatives; hydrophobically modified alkoxylated urethane polymers, such as PEG-l50/decyl alcohol/SMDI copolymer, PEG-l50/stearyl alcohol/SMDI copolymer, polyurethane-39; hydrophobically modified, alkali swellable emulsions, such as hydrophobically modified polypoly acrylates, hydrophobically modified polyacrylic acids, and hydrophobically modified polyacrylamides; hydrophobically modified polyethers.
  • These materials may have a hydrophobe that can be selected from cetyl, stearyl, oleayl, and combinations thereof, and a hydrophilic portion of repeating ethylene oxide groups with repeat units from 10-300, alternatively from 30-200, and alternatively from 40-150.
  • this class include PEG- l20-methylglucose dioleate, PEG-(40 or 60) sorbitan tetraoleate, PEG- 150 pentaerythrityl tetrastearate, PEG-55 propylene glycol oleate, PEG-150 distearate.
  • Non-limiting examples of additional rheology modifiers include acrylamide/ammonium acrylate copolymer (and)polyisobutene (and) polysorbate 20; acrylamide/sodium acryloyldimethyl taurate copolymer/ isohexadecane/ polysorbate 80; acrylates copolymer; acrylates/beheneth-25 methacrylate copolymer; acrylates/Cl0-C30 alkyl acrylate crosspolymer; acrylates/steareth-20 itaconate copolymer; ammonium polyacrylate/Isohexadecane/PEG-40 castor oil; C12-16 alkyl PEG-2 hydroxypropylhydroxyethyl ethylcellulose (HM-EHEC); carbomer; crosslinked polyvinylpyrrolidone (PVP); dibenzylidene sorbitol; hydroxyethyl ethylcellulose (EHEC); hydroxypropyl
  • Exemplary commercially-available rheology modifiers include ACULYNTM 28, Klucel M CS, Klucel H CS, Klucel G CS, SYLVACLEAR AF1900V, SYLVACLEAR PA1200V, Benecel E10M, Benecel K35M, Optasense RMC70, ACULYNTM33, ACULYNTM46, ACULYNTM22, ACULYNTM44, Carbopol Ultrez 20, Carbopol Ultrez 21, Carbopol Ultrez 10, Carbopol 1342, SepigelTM 305, SimulgelTM600, Sepimax Zen, and/or combinations thereof.
  • the leave-on treatment may comprise an aqueous carrier.
  • the formulations of the leave-on treatment can be in the form of pourable liquids (under ambient conditions).
  • Such compositions will therefore typically comprise an aqueous carrier, which is present at a level of at least 20 wt%, from about 20 wt% to about 95 wt%, or from about 60 wt% to about 85 wt%.
  • the aqueous carrier may comprise water, or a miscible mixture of water and organic solvent, and in one aspect may comprise water with minimal or no significant concentrations of organic solvent, except as otherwise incidentally incorporated into the composition as minor ingredients of other components.
  • the aqueous carriers useful in the leave-on treatment include water and water solutions of lower alkyl alcohols and polyhydric alcohols.
  • the lower alkyl alcohols useful herein are monohydric alcohols having 1 to 6 carbons, in one aspect, ethanol and isopropanol.
  • the polyhydric alcohols useful herein include propylene glycol, hexylene glycol, glycerin, and propane diol. pH
  • the hair care composition of the present invention may have a pH in the range from about 2 to about 10, at 25 °C. More preferably, the hair care composition may have a pH in the range of from about 2 to about 6, alternatively from about 3.5 to about 5, alternatively from about 5.25 to about 7.
  • the hair care composition described herein may optionally comprise one or more additional components known for use in hair care or personal care products, provided that the additional components are physically and chemically compatible with the essential components described herein, or do not otherwise unduly impair product stability, aesthetics or performance.
  • additional components are most typically those described in reference books such as the CTFA Cosmetic Ingredient Handbook, Second Edition, The Cosmetic, Toiletries, and Fragrance Association, Inc. 1988, 1992. Individual concentrations of such additional components may range from about 0.001 wt% to about 10 wt% by weight of the hair care compositions.
  • Non-limiting examples of additional components for use in the hair care compositions include conditioning agents, natural cationic deposition polymers, synthetic cationic deposition polymers, anti-dandruff agents, particles, suspending agents, paraffinic hydrocarbons, propellants, viscosity modifiers, dyes, non-volatile solvents or diluents (water-soluble and water-insoluble), pearlescent aids, foam boosters, additional surfactants or nonionic cosurfactants, pediculocides, pH adjusting agents, perfumes, preservatives, proteins, skin active agents, sunscreens, UV absorbers, and vitamins.
  • the hair care composition may comprise one or more conditioning agents.
  • Conditioning agents include materials that are used to give a particular conditioning benefit to hair.
  • the conditioning agents useful in the hair care compositions of the present invention typically comprise a water-insoluble, water-dispersible, non-volatile, liquid that forms emulsified, liquid particles.
  • Suitable conditioning agents for use in the hair care composition are those conditioning agents characterized generally as silicones , organic conditioning oils or combinations thereof, or those conditioning agents which otherwise form liquid, dispersed particles in the aqueous surfactant matrix.
  • One or more conditioning agents are present from about 0.01 wt% to about 10 wt%, from about 0.1 wt% to about 8 wt%, and from about 0.2 wt% to about 4 wt%, by weight of the composition.
  • the hair care compositions of the present invention may contain one or more silicone conditioning agents.
  • the silicones include dimethicones, dimethiconols, cyclic silicones, methylphenyl polysiloxane, and modified silicones with various functional groups such as amino groups, quaternary ammonium salt groups, aliphatic groups, alcohol groups, carboxylic acid groups, ether groups, epoxy groups, sugar or polysaccharide groups, fluorine-modified alkyl groups, alkoxy groups, or combinations of such groups.
  • Such silicones may be soluble or insoluble in the aqueous (or non-aqueous) product carrier.
  • the polymer can be in an emulsified form with droplet size of about 10 nm to about 30 micrometers
  • the conditioning agent of the compositions of the present invention may also comprise at least one organic conditioning material such as oil or wax, either alone or in combination with other conditioning agents, such as the silicones described above.
  • the organic material can be nonpolymeric, oligomeric or polymeric. It may be in the form of oil or wax and may be added in the formulation neat or in a pre-emulsified form.
  • organic conditioning materials include, but are not limited to: i) hydrocarbon oils; ii) polyolefins, iii) fatty esters, iv) fluorinated conditioning compounds, v) fatty alcohols, vi) alkyl glucosides and alkyl glucoside derivatives; vii) quaternary ammonium compounds; viii) polyethylene glycols and polypropylene glycols having a molecular weight of up to about 2,000,000 including those with CTFA names PEG-20 200, PEG-400, PEG-600, PEG- 1000, PEG-2M, PEG-7M, PEG-14M, PEG- 45M and mixtures thereof.
  • the hair care composition may further comprise one or more additional benefit agents.
  • the benefit agents comprise a material selected from the group consisting of anti-dandruff agents, anti fungal agents, anti-itch agents, anti-bacterial agents, anti-microbial agents, moisturization agents, anti-oxidants, vitamins, lipid soluble vitamins, perfumes, brighteners, enzymes, sensates, attractants, dyes, pigments, bleaches, and mixtures thereof.
  • the hair care compositions of the present invention may be presented in typical hair care formulations. They may be in the form of solutions, dispersion, emulsions, powders, talcs, encapsulated, spheres, spongers, solid dosage forms, foams, and other delivery mechanisms.
  • the hair care compositions may be provided in the form of a porous, dissolvable solid structure, such as those disclosed in U.S. Patent Application Publication Nos. 2009/0232873; and 2010/0179083, which are incorporated herein by reference in their entirety.
  • the hair care compositions comprise a chelant, a buffer system comprising an organic acid, from about 23% to about 75% surfactant; from about 10% to about 50% water soluble polymer; and optionally, from about 1% to about 15% plasticizer; such that the hair care composition is in the form of a flexible porous dissolvable solid structure, wherein said structure has a percent open cell content of from about 80% to about 100%.
  • the hair care compositions may be in the form of a viscous liquid comprising one or more aptomer, 20% surfactant and a polycarboxylate rheology modifier; wherein the polycarboxylate is specifically chosen to be effective at the high electrolyte levels resulting from the incorporation of the key buffer system and chelant used for this invention.
  • Non-limiting examples include acrylates/Cl0-C30 alkyl acrylate crosspolymers such as Carbopol EDT2020, 1342,1382, etc. from Lubrizol.
  • Rheology benefits of these actives may include stability, ease of dispensing, smoothness of spreading, etc.
  • the hair care compositions are generally prepared by conventional methods such as are known in the art of making the compositions. Such methods typically involve mixing of the ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, application of vacuum, and the like.
  • the compositions are prepared such as to optimize stability (physical stability, chemical stability, photostability) and/or delivery of the active materials.
  • the hair care composition may be in a single phase or a single product, or the hair care composition may be in a separate phases or separate products. If two products are used, the products may be used together, at the same time or sequentially. Sequential use may occur in a short period of time, such as immediately after the use of one product, or it may occur over a period of hours or days.
  • the following examples illustrate non- limiting examples of the invention described herein.
  • the exemplified hair care compositions can be prepared by conventional formulation and mixing techniques. It will be appreciated that other modifications of the hair care compositions within the skill of those in the formulation art can be undertaken without departing from the spirit and scope of this invention. All parts, percentages, and ratios herein are by weight unless otherwise specified. Some components may come from suppliers as dilute solutions. The amount stated reflects the weight percent of the active material, unless otherwise specified.
  • the library solution is then heated for 10 minutes at 95 °C and immediately placed in an iced ethanol bath for 15 min. Finally, the library is incubated at room temperature for 10 minutes, producing the snap cooled library used during selection. When needed, 50 pL of a commercial volume shampoo is added to the library.
  • the hair is sourced from Caucasian women as ponytails of length ⁇ 30cm from International Hair Importers (New York, USA). Prior to use for Aptamer selection each ponytail is washed three times in Pantene Silky Smooth Shampoo and Conditioner sourced from Japan.
  • the shampoo is added at 0. lg shampoo per g of hair and milked for 30 secs into the hair. This is then rinsed for 30 secs and repeated.
  • the conditioner is also added at O.lg conditioner per g of hair, milked for 30 secs and rinsed for 30 secs. This completed one complete cycle and is repeated three times. The hair is then left to dry overnight.
  • This method has been established to be suitable for studying the effects of oxidative treatments on hair by quantifying the amount of cysteic acid that is produced from oxidation of cystine (Strassburger, J., J. Soc. Cosmet. Chem., 36, 61-74 (1985); Joy, M. & Lewis, D.M., Int. J. Cosmet. Set, 13, 249-261 (1991); Signori, V. & Lewis, D.M., Int. J. Cosmet. Sci., 19, 1-13 (1997)).
  • a Perkin Elmer Spectrum® 1 Fourier Transform Infrared (FTIR) system equipped with a diamond Attenuated Total Internal Reflection (ATR) cell is used to measure the cysteic acid concentration in human hair.
  • FTIR Fourier Transform Infrared
  • ATR Attenuated Total Internal Reflection
  • Aptamer selection used one library aliquot containing about 10 15 sequences.
  • 50 pL of 10X selection buffer 100 mM HEPES, 1.2 M NaCl, 50 mM KC1, 50 mM MgCl2; pH 8.2
  • the library solution is snap cooled by heating the library for 10 minutes at 95 °C and immediately placing the solution in an iced ethanol bath for 15 min. Finally, the library is incubated at room temperature for 10 minutes, producing the snap cooled library used during selection.
  • an aliquot of 50 pL of a commercial volume shampoo clarifying shampoo, silicone free
  • Aptamer selection is performed on hair samples dipped into a solution containing the aptamer library.
  • a 3 cm long lock of hair held together by an elastic band and weighing approximately 0.03 g is placed into the snap cooled library solution.
  • the hair is incubated in the library solution for 20 minutes at room temperature. After incubation, the hair is removed and placed into a fresh 2 mL plastic Eppendorf tube containing 1 mL of selection buffer (100 mM HEPES, 1.2 M NaCl, 50 mM KC1, 50 mM MgCl2; pH 8.2) and placed on a rotator for 5 minutes.
  • selection buffer 100 mM HEPES, 1.2 M NaCl, 50 mM KC1, 50 mM MgCl2; pH 8.2
  • the hair is removed from the binding buffer and placed in a fresh 2 mL Eppendorf tube containing 1 mL of fresh selection buffer (100 mM HEPES, 1.2 M NaCl, 50 mM KC1, 50 mM MgCl2; pH 8.2) and is placed on a rotator for 5 minutes, resulting in two washes total.
  • fresh selection buffer 100 mM HEPES, 1.2 M NaCl, 50 mM KC1, 50 mM MgCl2; pH 8.2
  • the washed hair sample is then placed into a 2 mL Eppendorf tube containing 500 pL of 6 M Urea and incubated at 85 °C for 10 minutes. After heating, this first elution solution is recovered.
  • the hair is then placed into a fresh 2 mL Eppendorf tube containing 500 pL of fresh 6 M Urea and the sample is heated at 85°C for 10 minutes.
  • This second elution solution is recovered and combined with the first elution solution.
  • the DNA from the combined solution are purified using the GeneJET PCR Purification Kit (ThermoFisher Scientific, catalog # K0702) following manufacturer’s instructions.
  • the library is split into two channels. In channel B, selection is performed against tips of hair alone. In channel A, for each selection round, counter selection is performed against a clutch of hair from near the root, followed by positive selection against tip hair of the same sample. After 9 rounds of selection, the libraries from each channel are further split in 4 aliquots. Then, these sub-libraries are used to perform two more positive selection rounds against hair that is either severely damaged, moderately damaged, lightly damaged, or undamaged (root hair), as illustrated in Figure 1.
  • a lock of hair (length 3 cm, weight about 0.03 g) held together by an elastic band is placed into a 2 mL tube containing an aliquot of snap cooled library solution (500 pL), ensuring that the hair sample is fully submerged. The sample is incubated at room temperature for 20 minutes. The lock of hair is then removed, place into a new 2 mL tube containing 1 mL of IX selection buffer (10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4) and mixed for 5 minutes using a rotator to wash and remove unbound sequences from the hair sample. This cleaning step is repeated one more time.
  • IX selection buffer (10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4
  • the hair lock is placed into a new 2 mL tube containing 500 pL of 6 M Urea and incubated at 85 °C for 10 minutes to elute the bound sequences. This elution process is repeated and the two elution solutions are combined (1000 pL in total).
  • the eluted library is cleaned up with a GeneJET PCR Purification Kit (ThermoFisher Scientific, Catalog # K0702), following manufacturer's instructions.
  • the purified library is subjected to a test PCR where 5 pL of recovered library is PCR-amplified in increasing cycles to determine the optimum number of cycles through visualization on a 10% polyacrylamide gel (see table 1).
  • the PCR reactions are preformed using Standard Taq Polymerase Buffer (New England BioLabs, Catalog # B9014S), deoxyribonucleotide (dNTP) solution mix (New England BioLabs, Catalog # N0447L), 10 pM forward primer (5’- AACTACATGGTATGTGGTGAACT-3’ ) (TriLink, Catalog # NA), 10 pM reverse Primer (5’- GACGTACAATGTACCC -3’) (TriLink, Catalog # NA), and taq polymerase (New England BioLabs, Catalog # M0273X).
  • the full library is PCR amplified in several reaction tubes to produce the desired amount of DNA for the next selection round.
  • the amount of DNA library carried forward in each selection round is decreased by reducing the number of reaction tubes until a minimum of five reaction tubes is reached, increasing the aptamer selection stringency (see table 1).
  • the product of the PCR reactions is purified using the GeneJET PCR Purification Kit (ThermoFisher Scientific, Catalog # K0702).
  • RNAPol Reaction Buffer New England BioLabs, Catalog # M0251
  • Ribonucleotide Solution Set New England BioLabs, Catalog # N0450
  • RNase Inhibitor Murine
  • the DNA template and transcription solution are mixed and incubated for 16 hours at 37°C. Transcription creates RNA that is antisense to the selected library.
  • the DNA template is digested using DNase I (New England BioLabs - M0303, Canada). Then, the RNA is purified using the RNeasy MinElute Cleanup Kit (Qiagen, Catalog # 74204).
  • RNA yield is calculated using the A 26 o value, and the desired amount of RNA s reverse transcribed using the M-MuLV Reverse Transcriptase kit (New England BioLabs, Catalog # M0253) as well as 100 mM forward primer (5’- AACTACATGGTATGTGGTGAACT-3’) (TriLink, Catalog # NA), a deoxyribonucleotide (dNTP) solution mix (New England BioLabs, Catalog # N0447), and RNase inhibitor (New England BioLabs, Catalog # M0314).
  • the reverse transcription solution is carried forward into an RNase H reaction using an RNase H reaction kit (New England BioLabs, Catalog # M0297L), after which the solution is purified using the GeneJET PCR Purification Kit (ThermoFisher Scientific, Catalog # K0702). After purification, the produced single stranded sense DNA is used in the following selection round.
  • a pre- washed sample of hair is rinsed with three successive applications of 1 mL sterile HPLC-grade water.
  • the library solution (500 pL) and selection buffer (10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4) are pipetted into a tube and about 1 cm clutch of the hair is submerged into the tube.
  • the sample is incubated at 50 rpm, 37 °C, for 20 minutes.
  • the clutch of hair is removed and placed in a 2 mL tube containing 1 mL of IX selection buffer (10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4) and placed on a rotator at 50 rpm for 5 minutes. This wash is repeated 1 additional time.
  • the solution containing unbound DNA are combined and cleaned up with a GeneJET PCR Purification Kit (ThermoFisher Scientific, Catalog # K0702), followed by preparation for the positive selection experiment as described above (Example 1. Aptamer Design, A. Library Preparation).
  • Table 1 shows how aptamer selection progressed, the number of PCR cycles required to recover the aptamer library following the completion of a selection round, as well as how selection stringency increased between selection rounds by decreasing the number of reaction tubes and therefore the amount of library carried forward. TABLE 1. Summary of aptamer selection for hair root and hair tip
  • the recovered library from selection round 9 is amplified and split equally into 4 aliquots.
  • These split libraries are assigned to one of the following split sub-channels in each channel: severely damaged, moderately damaged, lightly damaged, and undamaged (root) hair samples.
  • the split rounds are carried out. Selection split rounds are performed as outlined in Table 2, where aptamers are selected based on their ability to bind to severely damaged, moderately damaged, lightly damaged, or undamaged (root hair) samples.
  • the selected libraries 7 to 9 in each channel as well as all the split selections against specific hair types are prepared for next generation sequencing (NGS) through a two-step PCR process.
  • NGS next generation sequencing
  • a different hex code (6 base sequence) and a portion of a universal sequencing primer is added to the 5’ end of each aptamer library.
  • complete universal sequencing primers are added to both ends.
  • the libraries are purified through acrylamide electrophoresis and balanced for relative quantity. These libraries are then pooled and sent to the Hospital for Sick Children in Toronto for NGS with an Illumina HiSeq instrument.
  • the sequencing data is tabulated and analyzed. A total of 96,464,333 sequences are analyzed and each library contained more than 2,000,000 different sequences (see Figure 2).
  • the sequences from selection round 9 within each channel are sorted by copy number and named in descending order with the highest copy number sequence being named H-Al for channel A and H- Bl for channel B. These top sequences are listed in Table 1.
  • the copy numbers of the top sequences of selection round 9 (Table 1) are determined on the libraries obtained from the other selection rounds. Finally, the frequency is computed for each sequence by dividing observed copy number by the total number of sequences observed in the particular library. Enrichment trajectories of the top 20 sequences in terms of frequency across different selection rounds are plotted (see Figures 3 and 4).
  • a covariance analysis for the change in sequence frequency is performed on the top 100 aptamers of channels A and B.
  • the frequency data is normalized by dividing the observed frequency of each aptamer by the average of the frequencies of the top 100 aptamers. This normalization allowed eliminating potential differences caused by PCR amplification prior to NGS analysis among different selection rounds.
  • the normalized values of each aptamer in selection round 7 are subtracted from the normalized values of the corresponding aptamer in selection rounds 8 to 11. The resulting matrix is used for the correlation analysis.
  • each cluster of covarying aptamers corresponds to a group of aptamers that bind to a different epitope within the hair.
  • An Euclidean distance matrix from the correlation matrix is generated and used as the basis for clustering with a Ward.D2 algorithm (see Figures 5 and 6). These analyses are performed with the software R.
  • aptamers H-Al, H-A2, H-Bl, and H-B2 are synthesized (Integrated DNA Technologies, Inc.) with a HEX fluorophore on the 5’ end and dissolved to a final concentration of 1 mM in water as a stock solution.
  • aptamers Five hair samples (2.5 mg of the tips, 3 cm in length) are incubated against each of the four aptamers at 50 nM in 1 mL of IX selection buffer (10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4) at room temperature for 30 minutes. The supernatant is removed and collected. Then, the hair samples are washed with IX selection buffer twice to remove any unbound aptamer and the supernatant is collected. Bound aptamers are then eluted by incubating the hair samples in a 6 M urea solution at 85 °C for 10 minutes.
  • IX selection buffer 10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4
  • solutions of different concentrations of the aptamers are tested to identify the saturation point for binding to the hair.
  • Solutions of 10 nM, 50 nM, and 100 nM aptamer in IX selection buffer (10 mM HEPES, 120 mM NaCl, 5 mM KC1, 5 mM MgCl2; pH 7.4) are incubated with hair samples using the same method described above. Amounts between 5% an 15% (in molar basis) of H-Al and H-B2 aptamers are bound to the hair tip samples. Based on this analysis, it is clear that the saturation concentration is about 50 nM for 2.5 mg of hair or 20 nM/mg (see Figure 8) and that a higher proportion of the aptamer is bound at a lower concentration (see Figure 9).
  • the frequency of motifs of six nucleotides from the random regions of the top four aptamers (H-Al, H-A2, H-Bl, and H-B2) within all the sequences of selection round 11 library (highly damaged hair only) is determined. Then, the average motif frequency is subtracted from the frequency of each motif and this value is divided by the standard deviation of all the motifs frequencies in that selection round, resulting in a Z value for every motif (see Figures 11, 13, 15, and 17). It stands to reason that sequences containing high frequency motifs may also bind to damaged hair.
  • FIGURE 12 The predicted secondary structures of aptamer H-Al and its conserved motifs.
  • N stands for any nucleotide
  • a search for common motifs within the top 10,000 sequences in terms of frequency from channels A and B is performed.
  • the lead motif identified in terms of significant deviation from random distribution is SEQ ID NO 213.
  • Oligonucleotides may comprise the motif SEQ ID NO 213.
  • Alignment of SEQ ID NO 1 to SEQ ID NO 200 is performed using the software Align X, a component of Vector NTI Advanced 11.5.4 by Invitrogen.
  • Align X a component of Vector NTI Advanced 11.5.4 by Invitrogen.
  • Several groups of sequences have at least 60% or at least 50% nucleotide sequence identity as illustrated in the alignments of Figure 19. In these alignments, only the central variable region of the aptamers is included for simplicity.
  • oligonucleotides with at least 50% or at least 60% nucleotide sequence identity to sequences may be selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200.
  • aptamers H-Al.l and H-A1.2 are derived from aptamer H-Al (see Figure 12).
  • H-Al.l comprises the top portion of the structure, while HA- 1.2 comprises most of the secondary structure (see Figure 20).
  • Aptamers H-A2.1 and H-A2.2 are derived from aptamer H- A2 (see Figure 14).
  • H-A2.1 comprises the middle portion of the structure, while H-A2.2 comprises the top of the structure (see Figure 21).
  • Aptamers H-Bl.l and H-B1.2 are derived from aptamer H- B1 (see Figure 16) and comprise the top portion of the structure (see Figure 22).
  • Aptamer H-B2.1 is derived from aptamer H-B2 (see Figure 18) and comprise the top portion of the structure (see Figure 23).
  • Table 3 provides binding results for each of these truncated aptamers with three hair samples. Hair sample #26 is analyzed twice with all truncated aptamers because this sample provided the highest binding affinity. These binding assays are performed and analyzed in a manner identical to that described previously for the full-length aptamers (see Example 3).
  • each aptamer for each hair sample is determined by comparing the binding value of the specific aptamer against the average binding value of all aptamers for the respective hair sample (see Table
  • truncated aptamers from HA-2 both truncations performed well with HA-2.1 performing better on the damaged hair sample #26.
  • the presence of the structure enabled by this motif is presumed to be responsible for the superior binding properties of this aptamer.
  • the truncated aptamer HB-1.1 performed better than the truncated aptamer HB-1.2. This improvement in performance is correlated with the presence of two conserved motifs in this aptamer versus only one of the conserved motifs in HB-1.2.
  • the binding performance of the truncated aptamer HB-2.1 demonstrates that this portion of the structure is all that is necessary to maintain the binding affinity of the full HB-2 aptamer.
  • EXAMPLE 7 Delivery of a Hair Care Active Ingredient with Aptamers.
  • Aptamers of the current invention are chemically synthesized.
  • a solution of a hair care active ingredient containing a free amine group (0.25 M) and imidazole (0.1 M) in water (pH 6) is prepared.
  • EDC l-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride
  • An aliquot of the amine/imidazole solution is added immediately to the reaction vial and vortexed until all the components are dissolved.
  • the produced modified aptamer conjugated with a hair care active ingredient can be formulated in hair care composition (e.g. shampoo or conditioner) to provide benefits when contacted with hair.
  • hair care composition e.g. shampoo or conditioner
  • An aptamer composition comprising at least one oligonucleotide consisting of: deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, and mixtures thereof; wherein said aptamer composition has a binding affinity for a material selected from the group consisting of: undamaged hair, damaged hair, hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, l8-methyleicosanoic acid, and mixtures thereof.
  • aptamer composition according to Paragraph A-C comprising at least one oligonucleotide selected from the group consisting of oligonucleotides with at least 50% nucleotide sequence identity to sequences selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200 and SEQ ID NO 214 to SEQ ID NO 220.
  • E The aptamer composition according to Paragraph A-D, comprising at least one oligonucleotide selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 200 and SEQ ID NO 214 to SEQ ID NO 220.
  • F The aptamer composition according to Paragraph A-E, comprising at least one oligonucleotide selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 101, SEQ ID NO 102, and SEQ ID NO 214 to SEQ ID NO 220.
  • aptamer composition according to Paragraph A-F wherein said at least one oligonucleotide comprises one or more motifs selected from the group consisting of SEQ ID NO 201 to SEQ ID NO 213.
  • aptamer composition according to Paragraph A-H, wherein said non-natural nucleobases are selected from the group comprising hypoxanthine, xanthine, 7- methylguanine, 5,6-dihydrouracil, 5-5-methylcytosine, 5-hydroxymethylcytosine, thiouracil, l-methylhypoxanthine, 6-methylisoquinoline-l-thione-2-yl, 3-methoxy-2- naphthyl, 5-propynyluracil-l-yl, 5-methylcytosin-l-yl, 2-aminoadenin-9-yl, 7-deaza-7- iodoadenin-9-yl, 7-deaza-7-propynyl-2-aminoadenin-9-yl, phenoxazinyl, phenoxazinyl-G- clam, and mixtures thereof.
  • said non-natural nucleobases are selected from the group comprising hypoxanthine,
  • aptamer composition according to Paragraph A-I wherein the nucleosides of said at least one oligonucleotide are linked by a chemical motif selected from the group comprising natural phosphate diester, chiral phosphorothionate, chiral methyl phosphonate, chiral phosphoramidate, chiral phosphate chiral triester, chiral boranophosphate, chiral phosphoroselenoate, phosphorodithioate, phosphorothionate amidate, methylenemethylimino, 3 '-amide, 3' achiral phosphoramidate, 3' achiral methylene phosphonates, thioformacetal, thioethyl ether, and mixtures thereof.
  • a chemical motif selected from the group comprising natural phosphate diester, chiral phosphorothionate, chiral methyl phosphonate, chiral phosphoramidate, chiral phosphate chiral triester,
  • aptamer composition according to Paragraph A-J where said derivatives of ribonucleotides or said derivatives of deoxyribonucleotides are selected from the group comprising locked oligonucleotides, peptide oligonucleotides, glycol oligonucleotides, threose oligonucleotides, hexitol oligonucleotides, altritol oligonucleotides, butyl oligonucleotides, L-ribonucleotides, arabino oligonucleotides, 2'-fluoroarabino oligonucleotides, cyclohexene oligonucleotides, phosphorodiamidate morpholino oligonucleotides, and mixtures thereof.
  • the aptamer composition according to Paragraph A-K further comprising at least one polymeric material, wherein said at least one polymeric material is covalently linked to said at least one oligonucleotide.
  • M The aptamer composition according to Paragraph A-L, wherein said at least one polymeric material is polyethylene glycol.
  • N The aptamer composition according to Paragraph A-M, wherein the nucleotides at the 5’- and 3’- ends of said at least one oligonucleotide are inverted.
  • P The aptamer composition according to Paragraph A-O, wherein the pyrimidine nucleotides of said at least one oligonucleotide are fluorinated at the 2’ position of the pentose group.
  • aptamer composition according to Paragraph A-P, wherein said at least one oligonucleotide is covalently or non-covalently attached to one or more hair care active ingredients; wherein said one or more hair care active ingredients are selected from the group comprising: conditioning agents, brightening agents, strengthening agents, anti fungal agents, anti-bacterial agents, anti-microbial agents, anti-dandruff agents, anti- malodor agents, perfumes, olfactory enhancement agents, anti-itch agents, cooling agents, anti-adherence agents, moisturization agents, smoothness agents, surface modification agents, antioxidants, natural extracts and essential oils, dyes, pigments, bleaches, nutrients, peptides, vitamins, enzymes, chelants, and mixtures thereof.
  • T The aptamer composition according to Paragraph A-S, wherein said at least one oligonucleotide is covalently or non-covalently attached to one or more nanomaterials.
  • a hair care composition according to Paragraph A-T comprising at least one nucleic acid aptamer; wherein said at least one nucleic acid aptamer has a binding affinity for a hair component.
  • hair care composition according to Paragraph A-U, wherein said hair component is selected from the group comprising: hair cuticle, hair epicuticle, hair exocuticle, hair endocuticle, hair cortex, hair keratins, hair F-layer, hair lipids, 18-methyleicosanoic acid, and mixtures thereof.
  • the hair care composition according to Paragraph A-V wherein said hair component is hair cuticle.
  • a method for delivering one or more hair care active ingredients to the hair according to Paragraph A-X comprising administering a hair care composition comprising at least one nucleic acid aptamer and one or more hair care active ingredients; wherein said at least one nucleic acid aptamer and said one or more hair care active ingredients are covalently or non-covalently attached; and wherein said at least one nucleic acid aptamer has a binding affinity for a hair component.
  • AA A method for delivering one or more hair care active ingredients to the hair according to
  • Paragraph A-Z comprises administering a hair care composition comprising: at least one nucleic acid aptamer and one or more nanomaterials; wherein said at least one nucleic acid aptamer and said one or more nanomaterials are covalently or non-covalently attached; and wherein said at least one nucleic acid aptamer has a binding affinity for a hair component.

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Abstract

La présente invention concerne une composition d'aptamères comprenant au moins un oligonucléotide consistant en : des désoxyribonucléotides, des ribonucléotides, des dérivés de désoxyribonucléotides, des dérivés de ribonucléotides et des mélanges de ceux-ci ; ladite composition d'aptamères présentant une affinité de liaison pour un matériau choisi dans le groupe constitué par : des cheveux non abîmés, des cheveux abîmés, une cuticule de cheveu, une épicuticule de cheveu, une exocuticule de cheveu, une endocuticule de cheveu, un cortex de cheveu, des kératines de cheveu, une couche F de cheveu, des lipides de cheveu, de l'acide 18-méthyleicosanoïque, et des mélanges de ceux-ci.
PCT/US2019/017151 2018-06-29 2019-02-08 Aptamères pour compositions de soin capillaire Ceased WO2020005325A1 (fr)

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MX2020014143A MX2020014143A (es) 2018-06-29 2019-02-08 Aptameros para aplicaciones de cuidado del cabello.
CN201980042900.3A CN112384622A (zh) 2018-06-29 2019-02-08 用于毛发护理应用的适配体
JP2020571775A JP2021529743A (ja) 2018-06-29 2019-02-08 ヘアケア用途のためのアプタマー
EP19707210.1A EP3814505A1 (fr) 2018-06-29 2019-02-08 Aptamères pour compositions de soin capillaire

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CN118234472A (zh) 2021-11-29 2024-06-21 宝洁公司 包含羟基肉桂酸的护肤组合物
JP2024541369A (ja) 2021-11-29 2024-11-08 ザ プロクター アンド ギャンブル カンパニー スキンケア組成物
CN121099982A (zh) 2023-05-15 2025-12-09 宝洁公司 包含羟基肉桂酸和烟酰胺衍生物的护肤组合物

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